An Update on Pertussis

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					                                                                     5/13/11	
  




        An	
  Update	
  on	
  Pertussis	
  

           Kathryn	
  M.	
  Edwards	
  MD	
  
      Sarah	
  H.	
  Sell	
  Professor	
  of	
  Pediatrics	
  	
  
    Vanderbilt	
  University	
  School	
  of	
  Medicine	
  




Bordetella pertussis attaching to ciliated epithelial cells




                         Objec4ves	
  
•  Epidemiology	
  and	
  Transmission	
  
   –  Disease	
  in	
  California	
  
   –  Infant	
  Disease	
  
   –  Adolescent	
  and	
  Adult	
  Disease	
  
•  PrevenIve	
  approaches	
  
   –  Universal	
  Adult	
  immunizaIon	
  
   –  Maternal	
  VaccinaIon	
  
   –  Neonatal	
  VaccinaIon	
  
   –  Cocooning	
  




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                                                               5/13/11	
  




          Bordetella	
  pertussis	
  
  Major	
  AnIgens	
  and	
  Virulence	
  Factors	
  

                           •  Pertussis	
  toxin	
  (PT)	
  
                           •  Filamentous	
  
                              hemaggluInin	
  (FHA)	
  
                           •  PertacIn	
  (PRN)	
  
                           •  Fimbrial	
  aggluInogens	
  
                              (FIM)	
  




Epidemiology	
  and	
  Transmission	
  




  The	
  Outbreak	
  in	
  California	
  	
  




                                                                       2	
  
                                                            5/13/11	
  




    Pertussis	
  in	
  California:	
  1947-­‐2010	
  	
  




Demographics	
  of	
  Pertussis	
  Outbreak	
  




                                                                    3	
  
                                                                                      5/13/11	
  




                                                 Pertussis	
  	
  Rates	
  
                                                   by	
  County	
  
                                                      2010	
  




                                                  hUp://www.cdph.ca.gov/healthinfo/
                                                  discond/pages/pertussis.aspx	
  




California	
  Pertussis	
  Cases:	
  	
  2010	
  	
  
 •    8383	
  confirmed,	
  probable	
  and	
  suspect	
  cases	
  	
  
 •    Rate	
  is	
  21.4	
  cases/100,000	
  popula4on	
  
 •    Most	
  cases	
  in	
  63	
  years	
  
 •    	
  Ten	
  deaths	
  to	
  date	
  
          – 9	
  infants	
  <2	
  months;	
  no	
  DTaP	
  doses	
  
          – 1	
  premature	
  infant,	
  age	
  2	
  months:	
  1	
  DTaP	
  	
  
          – Cough	
  illness	
  common	
  in	
  parents	
  or	
  sibs	
  




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5/13/11	
  




        5	
  
                                                                                                 5/13/11	
  




     What	
  is	
  the	
  Source	
  of	
  Infec4on	
  
                     for	
  Infants?	
  	
  




Epidemiologic	
  Features	
  of	
  Children	
  Hospitalized	
  
          with	
  Pertussis	
  in	
  Canada	
  
•  1082	
  cases	
  requiring	
  hospitalizaIon	
  	
  
•  92%	
  cases	
  in	
  children	
  <	
  I	
  year	
  of	
  age;	
  79%	
  in	
  children	
  
   <	
  6	
  months	
  of	
  age	
  
•  Mean	
  age	
  at	
  hospitalizaIon	
  12.4	
  weeks	
  
•  Ten	
  deaths	
  reported:	
  6	
  <	
  1	
  mo	
  of	
  age	
  
•  Source	
  of	
  infecIon	
  known	
  40%	
  of	
  cases;	
  sibling	
  
   (53%),	
  parent	
  (20%),	
  relaIve	
  (12%),	
  neighbor	
  (8%),	
  
   day	
  care	
  contact	
  (3%)	
  
•  Most	
  children	
  too	
  young	
  to	
  be	
  fully	
  vaccinated	
  
            Halperin	
  et	
  al.	
  Clin	
  Infect	
  Dis	
  1999;	
  28:	
  1238-­‐43	
  




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                                                                        5/13/11	
  




         Infant	
  Pertussis:	
  Who	
  Was	
  the	
  
                       Source?	
  
•  616	
  infant	
  cases	
  	
  
•  264	
  cases	
  source	
  idenIfied	
  




        Studies	
  of	
  Infec4on	
  Source	
  in	
  Children	
  	
  




   Wendelboe	
  PIDJ	
  2007	
  




                                                                                7	
  
                                                                                  5/13/11	
  




  Why	
  are	
  rates	
  of	
  adolescent	
  and	
  
    adult	
  disease	
  increasing?	
  	
  




 Rela4on	
  Between	
  Years	
  Since	
  Vaccina4on	
  and	
  
     A_ack	
  Rate	
  During	
  Pertussis	
  Outbreak	
  

    Interval in Years Since                                 Percent Infected
          Vaccination
  0-3 years                                                                21
  4-7 years                                                                47
  8-11 years                                                               65
  12 or more years                                                         95
  TOTAL                                                                    45


  Lambert. Public Health Report. 1965;80:365-9




  Establishment	
  of	
  Diagnos4c	
  Cutoff	
  Points	
  for	
  
                         Pertussis	
  
•  Measured	
  IgG	
  levels	
  against	
  PT,	
  FHA,	
  and	
  Fim	
  
   by	
  ELISA	
  in	
  sera	
  from	
  >6000	
  US	
  residents	
  (6-­‐49	
  
   years)	
  from	
  third	
  NaIonal	
  Health	
  and	
  
   NutriIon	
  ExaminaIon	
  Survey	
  
•  PopulaIon-­‐based	
  anIbody	
  levels	
  derived	
  
•  Established	
  diagnosIc	
  cut-­‐off	
  points	
  


          Baughman	
  et	
  al	
  Clin	
  Diag	
  Lab	
  Immunol	
  2004	
  




                                                                                          8	
  
                                                                                  5/13/11	
  




An4body	
  Titers	
  to	
  PT	
  in	
  Individuals	
  of	
  Various	
  Ages	
  




                                                                                          9	
  
5/13/11	
  




       10	
  
                                                            5/13/11	
  




Vaccine	
  Efficacy	
  in	
  the	
  APERT	
  Trial	
  
 2781	
  Subjects	
  Followed	
  for	
  2	
  Yrs	
  




  An4genic	
  Components	
  of	
  Diphtheria,	
  
Tetanus,	
  and	
  Acellular	
  Pertussis	
  Vaccines	
  




     Serologic	
  Responses	
  




                                                                   11	
  
                                                                                 5/13/11	
  




                          Pertussis	
  Incidence	
  and	
  	
  
                         Vaccine	
  Use,	
  1993	
  –	
  2004	
  
                       Canada’s	
  Northwest	
  Territories	
  




   Kandola K, et al. Can J Infect Dis Med Microbiol. 2005;16:271-274.




      New	
  CDPH	
  Tdap	
  Recommenda4ons:	
  
                       July	
  2010	
  
•  Immunize	
  pre-­‐teens,	
  teens	
  &	
  adults	
  with	
  Tdap	
  
    – 7-­‐9	
  year	
  olds	
  who	
  are	
  underimmunized	
  
    – >10	
  years	
  who	
  have	
  not	
  yet	
  received	
  Tdap	
  
         • Women	
  of	
  childbearing	
  age	
  	
  
         • Others	
  with	
  close	
  contact	
  with	
  infants	
  
         • Persons	
  >65	
  years	
  of	
  age	
  
•  No	
  minimum	
  interval	
  between	
  Td	
  and	
  Tdap	
  
•  Reminder	
  to	
  promptly	
  immunize	
  young	
  children	
  
   with	
  DTaP	
  	
  as	
  early	
  as	
  6	
  weeks	
  
             CDC:	
  MMWR	
  January	
  14,	
  2011	
  /	
  60(01):13-­‐15	
  




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                                                                                                    5/13/11	
  




          Maternal	
  Immuniza4on	
  




Maternal	
  Transfer	
  of	
  Pertussis	
  AnIbody	
  




   Van	
  Savage	
  J,	
  Decker	
  MD,	
  Edwards	
  KM,	
  Sell	
  SH,	
  Karzon	
  DT.	
  	
  
   J.	
  Infect.	
  Dis.	
  161:487,	
  1990	
  




                                                                                                           13	
  
                                                     5/13/11	
  




 Neonatal	
  Pertussis	
  	
  
 VaccinaIon	
  Study	
  




   Geometric	
  Mean	
  Titers	
  	
  	
  
      Halasha	
  et	
  al	
  J	
  Peds	
  2008	
  




Geometric	
  Mean	
  Titers	
  




                                                            14	
  
                                                        5/13/11	
  




Immune	
  Responses	
  to	
  Pertussis	
  An4gens	
  




                                                               15	
  
5/13/11	
  




       16	
  
                                                                 5/13/11	
  




                    Conclusions	
  
•  Pertussis	
  is	
  a	
  formidable	
  pathogen	
  
•  Adolescent	
  vaccines	
  are	
  being	
  used	
  
   and	
  appear	
  protecIve	
  where	
  studied	
  
•  Only	
  by	
  conInued	
  study	
  of	
  the	
  
   biology	
  and	
  changing	
  epidemiology	
  
   of	
  the	
  organism	
  will	
  we	
  aUain	
  control	
  




                                                                        17	
  

				
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